WO2000071121A1 - Microgranules gastroproteges, procede d'obtention et preparations pharmaceutiques - Google Patents

Microgranules gastroproteges, procede d'obtention et preparations pharmaceutiques Download PDF

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Publication number
WO2000071121A1
WO2000071121A1 PCT/FR2000/001367 FR0001367W WO0071121A1 WO 2000071121 A1 WO2000071121 A1 WO 2000071121A1 FR 0001367 W FR0001367 W FR 0001367W WO 0071121 A1 WO0071121 A1 WO 0071121A1
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WO
WIPO (PCT)
Prior art keywords
microgranules
layer
active
hydrophobic
microgranules according
Prior art date
Application number
PCT/FR2000/001367
Other languages
English (en)
French (fr)
Other versions
WO2000071121A9 (fr
Inventor
Bruno Criere
Pascal Suplie
Pascal Oury
Original Assignee
Laboratoires Des Produits Ethiques Ethypharm
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
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Priority to CA2373972A priority Critical patent/CA2373972C/fr
Priority to EEP200100615A priority patent/EE04902B1/xx
Priority to EP00929640A priority patent/EP1178799B1/fr
Priority to SK1632-2001A priority patent/SK287605B6/sk
Priority to JP2000619428A priority patent/JP5344781B2/ja
Priority to AT00929640T priority patent/ATE247960T1/de
Priority to AU47653/00A priority patent/AU771759B2/en
Priority to US09/979,146 priority patent/US8409612B1/en
Priority to BR0010832-4A priority patent/BR0010832A/pt
Priority to UA2001128863A priority patent/UA72522C2/uk
Priority to SI200030204T priority patent/SI1178799T1/xx
Priority to IL14648400A priority patent/IL146484A0/xx
Priority to EA200101221A priority patent/EA003943B1/ru
Priority to DE60004815T priority patent/DE60004815T2/de
Application filed by Laboratoires Des Produits Ethiques Ethypharm filed Critical Laboratoires Des Produits Ethiques Ethypharm
Priority to PL351658A priority patent/PL198355B1/pl
Priority to HU0201304A priority patent/HU227590B1/hu
Priority to DK00929640T priority patent/DK1178799T3/da
Priority to MXPA01011973A priority patent/MXPA01011973A/es
Publication of WO2000071121A1 publication Critical patent/WO2000071121A1/fr
Priority to NO20015480A priority patent/NO331643B1/no
Priority to IS6151A priority patent/IS2160B/is
Priority to BG106102A priority patent/BG65415B1/bg
Priority to IL146484A priority patent/IL146484A/en
Priority to HR20010940A priority patent/HRP20010940B1/xx
Publication of WO2000071121A9 publication Critical patent/WO2000071121A9/fr
Priority to HK02104416.6A priority patent/HK1042851B/zh

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5073—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings
    • A61K9/5078—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings with drug-free core
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the present invention relates to a pharmaceutical formulation of an inhibitor of the gastric proton pump, with the exception of Omeprazole.
  • This formulation is in the form of gastroprotected microgranules having improved stability over time
  • the present invention further extends to the process for manufacturing said microgranules, and to the pharmaceutical preparations containing them.
  • the gastric proton pump inhibitors within the scope of the present invention are derivatives of benzimidazole or thienimidazole, with the exception of omeprazole, as well as their pharmaceutically acceptable salts.
  • the proton pump inhibitors falling within the scope of the present invention in particular include Lansoprazole, Pantoprazole, Perprazole, Pa ⁇ prazole, Leminoprazole, Timoprazole and their pharmaceutically acceptable salts
  • Proton pump inhibitors are known for the treatment and prevention of diseases related to excessive secretion of gastric acid, such as esophagitis, gastritis, duodenitis, gastric ulcer and duodenal ulcer.
  • These compounds can also be used in patients undergoing AIDS therapy, and in patients suffering from gastroesophageal reflux disease or gastric disease.
  • these compounds are useful for the treatment of psoriasis and infections caused by Helicobacter.
  • the benzimidazole derivatives of the invention are compounds capable of degradation in an acidic or neutral medium, so that a formulation containing them must be
  • the present invention relates to a new gastroprotected formulation of a proton pump inhibitor containing at least two hydrophobic substances, the function of which is to '' improve the stability of the formulation during storage
  • Formulations containing a benzimidazole derivative and a hydrophobic substance already exist in the prior art, but this substance is not specifically used to increase the stability of the formulation.
  • these formulations contain alkaline compounds and / or tensio - ionic active ingredients
  • WO 96/01624 describes tablets of enté ⁇ que microgranules containing a proton pump inhibitor
  • the objective of the invention described is to prepare compressible microgranules without modifying the properties of their entene layer
  • the entene layer must contain plasticizers, such as polysorbates, PEGs and cetyl alcohol
  • the entene layer is for example made up of 74-80% of a methacry copolymer, 16-23% of methyl citrate and 1-3% of a mixture monoglyce ⁇ des / diglycé ⁇ des
  • WO 96/01624 describes the use of a particular plasticizer in the entene layer to improve the compressibility of the granules
  • the compositions described contain an ionic surfactant, such as sodium lauryl sulfate or an alkaline salt such as calcium phosphate
  • WO 97/12581 describes stable omeprazole granules devoid of any alkalizing compound
  • the entene layer comprises a plasticizer such as tnethylcitrate
  • the granules can contain lubricants, having hydrophobic properties
  • an ionic surfactant such as sodium lauryl sulfate, or crospovidone which has an alkaline character are associated with the active principle
  • WO 98/19668 describes omeprazole granules whose stability is improved by interposing a barrier layer between the entene coating and the active principle .
  • This barrier layer serves to protect the active principle from ambient humidity and enténque polymer with an acid character
  • This document does not suggest using a hydrophobic substance in the barrier layer, but it may contain Simethicone ® in a weight proportion of 0.4% compared to weight of the active ingredient Myvacet ® is used as a plasticizer in the entene layer
  • the granules consist of an alkaline core which may contain hydroxides or oxides of magnesium, calcium aluminum, t ⁇ sodium phosphate or magnesium trisilcate
  • WO 98/52564 describes granules of benzimidazole comprising an inert core coated with a layer containing the active principle associated with an alkaline substance, with a barrier layer consisting of a hydrophobic substance, and with an entene layer
  • the hydrophobic substance is a polyalkylsiloxane, a mineral oil isopropyl my ⁇ state, stearic acid or cetyl alcohol
  • the alkaline substance is for example ammonia, ammonium hydroxide or ammonium carbonate
  • WO 98/52564 proposes to improve the stability of benzimidazole granules by intercalating a hydrophobic film between the active principle and the entene coating and by associating an alkaline substance with the active principle
  • WO 96/31213 relates to a pasty oral formulation of a proton pump inhibitor for veterinary use or for persons having difficulty swallowing
  • This formulation is stable on long-term storage It contains a hydrophobic oily liquid vehicle and a hydrophobic thickening agent
  • the oily vehicle is for example Miglyol 810 ®
  • the thickening agent is cetostearyl alcohol, paraffin or hydrogenated castor oil
  • the formulation also contains alkalinizing agents, such as potassium sorbate or tethanolamine L ' teaching of this document is specific to a semi-solid formulation
  • EP 769 938 describes soft sustained-release capsules containing active substances which are unstable to humidity, to oxidation and to gastric fluid
  • EP 769 938 is limited to soft capsules which are not gastroprotected
  • a gastroprotected formulation of microgranules containing a benzimidazole derivative stable in storage devoid of alkaline substances and containing a hydrophobic substance both in the active layer and in the entene layer
  • the aim of the present The invention is to provide a gastroprotected formulation of microgranules of a gastric proton pump inhibitor, with the exception of Omeprazole whose stability in long-term storage is improved, and which also has the desired therapeutic properties. , that is to say a certain resistance to dissolution in an acid medium, and rapid solubility in a neutral medium
  • the present invention relates to a new gastroprotected formulation of a proton pump inhibitor, with the exception of Omeprazole containing several hydrophobic substances chosen to increase the stability of the active principle while obtaining the desired dissolution profile.
  • alkaline compounds ie whose pH is greater than or equal to 7, for example, amino bases such as ammonia, t ⁇ ethanolamine, salts of carboxylic acids such as sodium citrate or potassium sorbate, carbonates phosphates, hydroxides or oxides of sodium, aluminum, potassium, magnesium or calcium, magnesium silicate, t ⁇ s (hydroxymethyl) aminomethane, natural clays such as montmo ⁇ llonite, sodium glycerophosphate, sodium borate, organic buffers, crospovidone,
  • amino bases such as ammonia, t ⁇ ethanolamine
  • salts of carboxylic acids such as sodium citrate or potassium sorbate
  • carbonates phosphates hydroxides or oxides of sodium, aluminum, potassium, magnesium or calcium, magnesium silicate, t ⁇ s (hydroxymethyl) aminomethane
  • natural clays such as montmo ⁇ llonite, sodium glycerophosphate, sodium borate, organic buffers, crospovidone,
  • ionic surfactants such as lauryl sulfate
  • microgranules according to the invention contain an inhibitor of the gastric proton pump with the exception of Omeprazole, and each comprise an active layer containing the active principle and an external gastroprotection layer. They are characterized in that the active layer and the gastroprotection layer each contain at least one hydrophobic substance chosen to increase the stability of microgranules during storage.
  • the microgranules of the invention are devoid of any alkaline compound and of any ionic surfactant Hydrophobic substances which do not chemically react with the principle will be chosen active which can be easily implemented during formulation and which are compatible with the excipients used
  • hydrophobic substance means any substance making it possible to obtain a gain in stability of the microgranules during storage, in particular any substance having an HLB of less than 15, or non-hygroscopic or practically insoluble in water, or forming a film not permeable to water vapor
  • the hydrophobic substance preferably represents between 5 and 40% by weight of the active principle. It is advantageously chosen from silicone oils.
  • the active layer comprises advantageously a binder chosen from pharmaceutically acceptable binders, for example hydroxypropyl methylcellulose whose mass proportion preferably represents 30 to 50% relative to the weight of active principle
  • the external gastroprotection layer advantageously consists of a gastroprotective film-forming agent, a hydrophobic substance and a hydrophilic plasticizer.
  • the hydrophobic substance contained in the gastroprotection layer is chosen from waxes, oils and their mixtures often used in the pharmaceutical industry, preferably glycends, for example Gelucire® in proportion of 5 to 20% of the dry varnish of the film-forming agent
  • the plasticizer is chosen from pharmaceutically acceptable plasticizers, for example PEG cetyl alcohol or triethyl citrate.
  • the plasticizer represents from 5 to 20%, advantageously 10%, of the dry varnish weight of the film-forming agent.
  • the gastroprotective film-forming agent is advantageously a copolymer of methacrylic acid such as Eudragit L30D®, at a rate of 15 to 60%. dry deposition of polymer relative to the mass of microgranules.
  • a lubricating agent chosen from pharmaceutically acceptable lubricants, advantageously talc, is optionally used.
  • the gastroprotection layer advantageously consists of 90 to 95%) of film-forming agent, and of an equal amount of plasticizer and hydrophobic substance.
  • At least one intermediate layer is interposed between the active layer and the gastroprotection layer.
  • the intermediate layer may also contain a hydrophobic substance, which preferably represents between 5 and 40% by weight of the active principle.
  • the intermediate layer may contain a diluting substance or a coating agent associated with a hydrophobic plasticizer.
  • microgranules according to the invention comprise:
  • An active ingredient layer containing an active ingredient, a binder chosen from pharmaceutically acceptable binders, a hydrophobic substance and a nonionic surfactant,
  • the first intermediate protective layer advantageously comprises mannitol (which is non-hygroscopic) in mass proportion of 100 to 300% and, preferentially, 200% of the weight of the active principle.
  • This layer also comprises a binder chosen from pharmaceutically acceptable binders, advantageously hydroxypropylmethylcellulose, in a proportion of 10 to 30% and, preferably, 20% of the weight of mannitol.
  • a binder chosen from pharmaceutically acceptable binders, advantageously hydroxypropylmethylcellulose, in a proportion of 10 to 30% and, preferably, 20% of the weight of mannitol.
  • this protective layer may be included in this protective layer a lubricant chosen from pharmaceutically acceptable lubricants, in this case talc (which is non-hygroscopic) in proportion less than 100% of the weight of the active principle
  • a lubricant chosen from pharmaceutically acceptable lubricants, in this case talc (which is non-hygroscopic) in proportion less than 100% of the weight of the active principle
  • the second protective layer is constituted a water-soluble coating agent chosen from pharmaceutically acceptable film-forming agents, advantageously hydroxypropylmethylcellulose, in a proportion of 1 to 10%> preferably 5% of the weight of microgranules obtained after assembly of the first protective layer
  • a hydrophobic plasticizer such as Myvacet® will be used in a proportion of 10 to 30% of the dry varnish of the coating agent retained.
  • the second protective layer may contain a lubricating agent chosen from pharmaceutically acceptable lubricants such as talc, in a proportion of 10 to 50%, preferably 15% by weight of the dry varnish of the coating agent retained.
  • a lubricating agent chosen from pharmaceutically acceptable lubricants such as talc, in a proportion of 10 to 50%, preferably 15% by weight of the dry varnish of the coating agent retained.
  • the active layer is mounted on a neutral core consisting for example of sucrose and starch, whose diameter is between 200 and 900 microns
  • the microgranules according to the invention preferably have a particle size of between 0.3 and 3 mm, more preferably between 0.4 and 2 mm
  • microgranules of the invention comprise:
  • the present invention also relates to a process for preparing the microgranules according to the invention. This process is characterized in that it is carried out in an aqueous medium, without the use of any organic solvent.
  • microgranules described in the present invention will be obtained by using any equipment suitable for the preparation and coating of microgranules, well known to those skilled in the art and, in particular, equipment of the conventional turbine, perforated turbine or bed type type. fluidized air
  • the microgranules according to the invention are obtained by mounting on a neutral core, preferably in a fluidized air bed, by successive sprays
  • the microgranules according to the invention are mounted on a neutral core in a fluidized air bed, by successive sprays.
  • Each spraying step is advantageously followed by sieving and drying at a temperature below the melting temperature of each of the compounds forming part of the microgranules in said step.
  • microgranules obtained according to this process advantageously contain less than 1.5%, preferably 0.5% by weight of water.
  • the present invention finally relates to pharmaceutical preparations containing the microgranules according to the invention capable of being obtained by the process described above, these preparations will advantageously be in the form of capsules containing approximately 5 to 60 mg of active principle
  • Microgranules are prepared in an OHLMAN type fluidized air bed apparatus, of the following composition
  • the purified water is stirred and the Pharmacoat 603® (manufactured by SEPPIC), Polysorbate 80® (manufactured by SEPPIC), Dimethicone® (manufactured by LAMBERT and RIVIERE) and the active ingredient are added successively.
  • Pharmacoat 603® manufactured by SEPPIC
  • Polysorbate 80® manufactured by SEPPIC
  • Dimethicone® manufactured by LAMBERT and RIVIERE
  • a preassembly suspension consisting of 4% by weight of Pharmacoat 603®, 20% by weight of Mannitol 25® (both manufactured by ROQUETTE) and 76% of purified water is prepared.
  • the pre-assembled neutrals are then sieved and dried for one to four hours at approximately 50 ° C.
  • This pre-assembly step is carried out under the same conditions as the Pharmacoat® / Mann ⁇ tol pre-assembly step.
  • the temperature of the granules is maintained between 26 and 28 ° C. during the spraying of the suspension.
  • the coated microgranules are then sieved and dried to approximately
  • microgranules obtained have the following properties •

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  • Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • Dermatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
PCT/FR2000/001367 1999-05-21 2000-05-19 Microgranules gastroproteges, procede d'obtention et preparations pharmaceutiques WO2000071121A1 (fr)

Priority Applications (24)

Application Number Priority Date Filing Date Title
EEP200100615A EE04902B1 (et) 1999-05-21 2000-05-19 Mikrograanul, selle valmistamismeetod ja farmatseutiline preparaat
DE60004815T DE60004815T2 (de) 1999-05-21 2000-05-19 Gegen magensaft geschützte omeprazol-mikrogranülen, herstellungsverfahren und pharmazeutische zubereitungen
EA200101221A EA003943B1 (ru) 1999-05-21 2000-05-19 Защищенные от растворения желудочным соком микрогранулы, способ получения и фармацевтические препараты
SK1632-2001A SK287605B6 (sk) 1999-05-21 2000-05-19 Mikrogranuly obsahujúce inhibítor žalúdočnej protónovej pumpy, spôsob ich prípravy a farmaceutické prostriedky s ich obsahom
JP2000619428A JP5344781B2 (ja) 1999-05-21 2000-05-19 胃液において不溶性の微小顆粒、その調製方法、および薬学的調製物
AT00929640T ATE247960T1 (de) 1999-05-21 2000-05-19 Gegen magensaft geschützte omeprazol- mikrogranülen, herstellungsverfahren und pharmazeutische zubereitungen
AU47653/00A AU771759B2 (en) 1999-05-21 2000-05-19 Microgranules insoluble in gastric fluid, method for obtaining same and pharmaceutical preparations
US09/979,146 US8409612B1 (en) 1999-05-21 2000-05-19 Microgranules insoluble in gastric fluid, method for obtaining same and pharmaceutical preparations
BR0010832-4A BR0010832A (pt) 1999-05-21 2000-05-19 Microgrânulos contendo um inibidor da bomba de prótons gástrica, processo de preparação dos microgrânulos, e, preparações farmacêuticas
UA2001128863A UA72522C2 (en) 1999-05-21 2000-05-19 Microgranules insoluble in gastric fluid, method of manufacture and pharmaceutical formulation
SI200030204T SI1178799T1 (en) 1999-05-21 2000-05-19 Microgranules insoluble in gastric fluid, method for obtaining same and pharmaceutical preparations
IL14648400A IL146484A0 (en) 1999-05-21 2000-05-19 Microgranules insoluble in gastric fluid, method for obtaining same and pharmaceutical preparations
EP00929640A EP1178799B1 (fr) 1999-05-21 2000-05-19 Microgranules gastroproteges, procede d'obtention et preparations pharmaceutiques
CA2373972A CA2373972C (fr) 1999-05-21 2000-05-19 Microgranules gastroproteges, procede d'obtention et preparations pharmaceutiques
MXPA01011973A MXPA01011973A (es) 1999-05-21 2000-05-19 Microgranulos gastroprotegidos, metodo de obtencion y preparaciones farmaceuticas.
PL351658A PL198355B1 (pl) 1999-05-21 2000-05-19 Mikrogranulki zawierające inhibitor żołądkowej pompy protonowej, sposób ich wytwarzania oraz preparat farmaceutyczny
HU0201304A HU227590B1 (hu) 1999-05-21 2000-05-19 Gyomornedvben oldhatatlan mikrogranulátumok, elõállításuk és az ezeket tartalmazó gyógyszerkészítmények
DK00929640T DK1178799T3 (da) 1999-05-21 2000-05-19 Gastrobeskyttede mikrogranula, fremgangsmåde til opnåelse af samme og farmaceutiske præparater
IS6151A IS2160B (is) 1999-05-21 2001-11-08 Örkorn óleysanleg í magavökva, aðferð til að aflaþeirra og lyfjaefnablöndur
NO20015480A NO331643B1 (no) 1999-05-21 2001-11-08 Mikrogranuler som ikke er loselige i magesaft, fremgangsmater for a oppna det samme og farmasoytiske preparater
BG106102A BG65415B1 (bg) 1999-05-21 2001-11-13 Микрогранули, неразтворими в стомашния сок, методза тяхното получаване и фармацевтични препарати
IL146484A IL146484A (en) 1999-05-21 2001-11-13 Insoluble microgranols in gastric fluid, method of manufacture and pharmaceutical preparations
HR20010940A HRP20010940B1 (en) 1999-05-21 2001-12-20 Microgranules insoluble in gastric fluid, method for obtaining same and pharmaceutical preparations
HK02104416.6A HK1042851B (zh) 1999-05-21 2002-06-12 不溶於胃液的微粒，獲得此微粒的方法和藥製劑

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
FR99/06479 1999-05-21
FR9906479A FR2793688B1 (fr) 1999-05-21 1999-05-21 Microgranules gastroproteges, procede d'obtention et preparations pharmaceutiques

Publications (2)

Publication Number Publication Date
WO2000071121A1 true WO2000071121A1 (fr) 2000-11-30
WO2000071121A9 WO2000071121A9 (fr) 2002-05-23

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PCT/FR2000/001367 WO2000071121A1 (fr) 1999-05-21 2000-05-19 Microgranules gastroproteges, procede d'obtention et preparations pharmaceutiques

Country Status (35)

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US (1) US8409612B1 (cs)
EP (1) EP1178799B1 (cs)
JP (2) JP5344781B2 (cs)
KR (1) KR100603915B1 (cs)
CN (1) CN1243546C (cs)
AR (1) AR024036A1 (cs)
AT (1) ATE247960T1 (cs)
AU (1) AU771759B2 (cs)
BG (1) BG65415B1 (cs)
BR (1) BR0010832A (cs)
CA (1) CA2373972C (cs)
CZ (1) CZ302946B6 (cs)
DE (1) DE60004815T2 (cs)
DK (1) DK1178799T3 (cs)
EA (1) EA003943B1 (cs)
EE (1) EE04902B1 (cs)
ES (1) ES2204598T3 (cs)
FR (1) FR2793688B1 (cs)
GE (1) GEP20053580B (cs)
HK (1) HK1042851B (cs)
HR (1) HRP20010940B1 (cs)
HU (1) HU227590B1 (cs)
IL (2) IL146484A0 (cs)
IS (1) IS2160B (cs)
MX (1) MXPA01011973A (cs)
NO (1) NO331643B1 (cs)
PL (1) PL198355B1 (cs)
PT (1) PT1178799E (cs)
RS (1) RS50241B (cs)
SI (1) SI1178799T1 (cs)
SK (1) SK287605B6 (cs)
TR (1) TR200103325T2 (cs)
UA (1) UA72522C2 (cs)
WO (1) WO2000071121A1 (cs)
ZA (1) ZA200109472B (cs)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004096218A2 (en) * 2003-04-29 2004-11-11 Laboratorios Belmac, S.A. Pellet formulations of acid-labile antiulcer benzimidazole compounds

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* Cited by examiner, † Cited by third party
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FR2821745B1 (fr) * 2001-03-09 2004-07-02 Ethypharm Lab Prod Ethiques Granules et granules enrobes au gout masque
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